An access port for a reaction vessel is presented which is useful with solid phase chemical synthesis or other chemistry, clinical or biological fluid handling operations which require a fluid containment vessel which is chemically inert, provides for control of the internal atmosphere and temperature, facilitates mixing, provides for accurate and facile addition of fluids as well as filtered removal of fluid from the vessel and is suitable for automation.
The inlet and outlet ports for fluid addition and removal are a critical features of the design of a reaction vessel, since maintaining the integrity of the inert or reactive atmosphere and retaining any solid support, such as resin inside the vessel, is critical.
In some designs, fluid enters the top of the vessel and drains out the bottom of the vessel through manually operated valves. Solids are maintained inside the vessel by placing a frit at the bottom of the vessel which serves as a filter which passes fluid only. This type of valving arrangement is suitable for a small number of reaction vessels but is impractical for automatic filling and draining of an array of vessels.
One design approach, suitable for automation, is to replace the top valve with a septum and add fluid by piercing the septum with a dispensing canula. The bottom valve may be replaced with a u-tube which will drain the vessel when sufficient head pressure is applied to cause a siphon. However, with this design, the u-tube outlet port can prematurely drain if pressures build up inside the reaction vessel during heating operations. Also, since the outlets feed into a common waste manifold, there is no way to monitor a blockage of the outlet of an individual reaction vessel. This vessel design is expensive to build, difficult to change frits, and require vessels with bottom seals.
In order to overcome the problems associated with the vessels which have been previously reported, a novel vessel should be well suited for automatic filling and draining operations using conventional pipetting equipment or other robotic or automation equipment. In addition, the septum access port should be usable with practically any type and size vessel, including but not limited to test tubes, vials, beakers, flasks, jars and 96-well plate. Further the vessel should not have a bottom drain port since this restricts direct heating and cooling of the vessels and with a smooth bottom, heating and cooling may be effected by direct application of a hot stage or cooling reservoir to the vial. The vessels should operate under an inert atmosphere with no fluid loss. That is, higher inert gas pressures could be used if the top of a sipper tube and the fluid in the vessel always have the same applied pressure. In the event of a leak in the septum due to multiple piercing of an aspirating or dispensing canula, the contents of the vessel should be contained and not leak. Any applied inert or reactive gas should bleed or vent out a predetermined hole, while maintaining the vessel under an inert gas atmosphere and assuring retention of the liquid in the vessel. The optimum design should not have check valves, u-tubes, or o-rings which decrease the reliability and increase the cost of manufacturing arrays of reaction wells. Automatic back flushing of any filtering frits should be provided as this will reduce the chance of frit or filter blockage. The design should also provide for the draining of each vessel individually when used in a multi-vessel array, as this would increase the vacuum capacity available for this operation. Such a device could also permit incorporation of sensors in the aspiration or dispensing canula which would insure an individual vessel was properly drained.